The axon is generally a long cellular process dependent for its viability upon its continuity with the cell body for continuous supply of macromolecules and metabolites. Nonetheless, there is strong circumstantial evidence that the myelinated axon has the capacity to synthesize proteins locally. The purpose of the proposed research is to evaluate the role of local axonal protein synthesizing activity in the renewal and growth processes of the vertebrate myelinated axon. This aim will be pursued by: (1) identifying protein products synthesized intraaxonally in selected myelinated normal axons of the peripheral and central nervous system, in traumatized regions of neurotomized nerves and in actively regenerating axons in vitro; (2) studying the disposition and metabolic fate of the products synthesized in the axon locally in vivo; (3) studying local protein synthesis and identifying products synthesized in growing neurites of immature neurons in tissue culture in order to compare them to regenerating axons of the adult; (4) characterizing macromolecular RNA classes present in the axon; and (5) developing an in vivo cell-free, myelin-free axon system capable of protein synthesis in order to study factors that may control axonal protein synthesis. The approach will be primarily microanalytical biochemistry, in which histological purity of axon samples from nerves and tissue will be assured.